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Recent studies suggest an increased risk of reinfection with the SARS-CoV-2 Omicron variant compared with previous variants, potentially due to an increased ability to escape immunity specific to older variants, high antigenic divergence of Omicron from earlier virus variants as well as its altered cell entry pathway. The present study sought to investigate epidemiological evidence for differential SARS-CoV-2 reinfection intervals and incidence rates for the Delta versus Omicron variants within Wales. Reinfections in Wales up to February 2022 were defined using genotyping and whole genome sequencing. The median inter-infection intervals for Delta and Omicron were 226 and 192 days, respectively. An incidence rate ratio of 2.17 for reinfection with Omicron compared to Delta was estimated using a conditional Poisson model, which accounted for several factors including sample collection date, age group, area of residence, vaccination and travel status. These findings are consistent with an increased risk of reinfection with the Omicron variant, and highlight the value of monitoring emerging variants that have the potential for causing further waves of cases.

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Background: The COVID-19 pandemic and the ensuing implementation of control measures caused widespread societal disruption. These disruptions may also have affected community transmission and seasonal circulation patterns of endemic respiratory viruses. Objective: We aimed to investigate the impact of COVID-19-related disruption on influenza-related emergency hospital admissions and deaths in Wales in the first 2 years of the pandemic. Methods: A descriptive analysis of influenza activity was conducted using anonymized pathology, hospitalization, and mortality data from the Secure Anonymised Information Linkage Databank in Wales. The annual incidence of emergency hospitalizations and deaths with influenza-specific diagnosis codes between January 1, 2015, and December 31, 2021, was estimated. Case definitions of emergency hospitalization and death required laboratory confirmation with a polymerase chain reaction test. Trends of admissions and deaths were analyzed monthly and yearly. We conducted 2 sensitivity analyses by extending case definitions to include acute respiratory illnesses with a positive influenza test and by limiting admissions to those with influenza as the primary diagnosis. We also examined yearly influenza testing trends to understand changes in testing behavior during the pandemic. Results: We studied a population of 3,235,883 Welsh residents in 2020 with a median age of 42.5 (IQR 22.9-61.0) years. Influenza testing in Wales increased notably in the last 2 months of 2020, and particularly in 2021 to 39,720 per 100,000 people, compared to the prepandemic levels (1343 in 2019). The percentage of influenza admissions matched to an influenza polymerase chain reaction test increased from 74.8% (1890/2526) in 2019 to 85.2% (98/115) in 2021. However, admissions with a positive test per 100,000 population decreased from 17.0 in 2019 to 2.7 and 0.6 in 2020 and 2021, respectively. Similarly, deaths due to influenza with a positive influenza test per 100,000 population decreased from 0.4 in 2019 to 0.0 in 2020 and 2021. Sensitivity analyses showed similar patterns of decreasing influenza admissions and deaths in the first 2 years of the COVID-19 pandemic. Conclusions: Nonpharmaceutical interventions to control COVID-19 were associated with a substantial reduction in the transmission of the influenza virus, with associated substantial reductions in hospital cases and deaths observed. Beyond the pandemic context, consideration should be given to the role of nonpharmaceutical community-driven interventions to reduce the burden of influenza.

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BACKGROUND: Pleural disease is common, representing 5% of the acute medical workload, and its incidence is rising, partly due to the ageing population. Frailty is an important feature and little is known about disease progression in patients with frailty and pleural disease. We aimed to examine the effect of frailty on mortality and other relevant outcomes in patients diagnosed with pleural disease. METHODS: In this cohort study in Wales, the national Secure Anonymised Information Linkage databank was used to identify a cohort of individuals diagnosed with non-malignant pleural disease between Jan 1, 2005, and March 1, 2023, who were not known to have left Wales. Frailty was assessed at diagnosis of pleural disease using an electronic Frailty Index. The primary outcome was time from diagnosis to all-cause mortality for all patients. Data were analysed using multilevel mixed-effects Cox proportional hazards regression adjusting for the prespecified covariates of age, sex, Welsh Index of Multiple Deprivation quintile, smoking status, comorbidity, and subtype of pleural disease. FINDINGS: 54 566 individuals were included in the final sample (median age 66 years [IQR 47-77]; 26 477 [48·5%] were female and 28 089 [51·5%] were male). By the end of the study period, 25 698 (47·1%) participants had died, with a median follow-up of 1·0 years (IQR 0·2-3·6). There was an association between frailty and all-cause mortality, which increased as frailty worsened. Compared with fit individuals, there was increasing mortality for those with mild frailty (adjusted hazard ratio 1·11 [95% CI 1·08-1·15]; p<0·0001), moderate frailty (1·25 [1·20-1·31]; p<0·0001), and severe frailty (1·36 [1·28-1·44]; p<0·0001). INTERPRETATION: Independent of age and comorbidities, frailty status at diagnosis of pleural disease appeared to be useful as a prognostic indicator. Patients with moderate or severe frailty had a rapid decline in health. Future patients should be assessed for frailty at the time of diagnosis of pleural disease and might benefit from optimised care and advance care planning. FUNDING: Cardiff University's Wellcome Trust iTPA funding award.

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BACKGROUND: Despite the considerable morbidity caused by recurrent urinary tract infections (rUTIs), and the wider personal and public health implications from frequent antibiotic use, few studies adequately describe the prevalence and characteristics of women with rUTIs or those who use prophylactic antibiotics. AIM: To describe the prevalence, characteristics, and urine profiles of women with rUTIs with and without prophylactic antibiotic use in Welsh primary care. DESIGN AND SETTING: This was a retrospective cross-sectional study in Welsh general practice using the Secure Anonymised Information Linkage (SAIL) Databank. METHOD: The characteristics of women aged ≥18 years with rUTIs or using prophylactic antibiotics from 2010 to 2020, and associated urine culture results from 2015 to 2020, are described. RESULTS: In total, 6.0% (n = 92 213/N = 1 547 919) had rUTIs, and 1.7% (n = 26 862/N = 1 547 919) were prescribed prophylactic antibiotics with the rates increasing after 57 years of age. Only 49.0% (n =13 149/N = 26 862) of users of prophylactic antibiotics met the definition of rUTIs before initiation. The study found that 80.8% (n = 44 947/N = 55 652) of women with rUTIs had a urine culture result in the preceding 12 months with high rates of resistance to trimethoprim and amoxicillin. Of women taking prophylactic antibiotics, 64.2% (n = 9926/N = 15 455) had a urine culture result before initiation and 18.5% (n = 320/N = 1730) of women prescribed trimethoprim had resistance to it on the antecedent sample. CONCLUSION: A substantial proportion of women had rUTIs or incident prophylactic antibiotic use. However, 64.2% (n = 9926/N = 15 455) of women had urine cultured before starting prophylaxis. There was a high proportion of cultured bacteria resistant to two antibiotics used for rUTI prevention and evidence of resistance to the prescribed antibiotic. More frequent urine cultures for rUTI diagnosis and before prophylactic antibiotic initiation could better inform antibiotic choices.

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Understanding the drivers of respiratory pathogen spread is challenging, particularly in a timely manner during an ongoing epidemic. In this work, we present insights that we obtained using daily data from the National Health Service COVID-19 app for England and Wales and that we shared with health authorities in almost real time. Our indicator of the reproduction number R(t) was available days earlier than other estimates, with an innovative capability to decompose R(t) into contact rates and probabilities of infection. When Omicron arrived, the main epidemic driver switched from contacts to transmissibility. We separated contacts and transmissions by day of exposure and setting and found pronounced variability over days of the week and during Christmas holidays and events. For example, during the Euro football tournament in 2021, days with England matches showed sharp spikes in exposures and transmissibility. Digital contact-tracing technologies can help control epidemics not only by directly preventing transmissions but also by enabling rapid analysis at scale and with unprecedented resolution.

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BACKGROUND: Socioeconomic mortality inequalities are persistent in Europe but have been changing over time. Smoking is a known contributor to inequality levels, but knowledge about its impact on time trends in inequalities is sparse. METHODS: We studied trends in educational inequalities in smoking-attributable mortality (SAM) and assessed their impact on general mortality inequality trends in England and Wales (E&W), Finland, and Italy (Turin) from 1972 to 2017. We used yearly individually linked all-cause and lung cancer mortality data by educational level and sex for individuals aged 30 and older. SAM was indirectly estimated using the Preston-Glei-Wilmoth method. We calculated the slope index of inequality (SII) and performed segmented regression on SIIs for all-cause, smoking and non-SAM to identify phases in inequality trends. The impact of SAM on all-cause mortality inequality trends was estimated by comparing changes in SII for all-cause with non-SAM. RESULTS: Inequalities in SAM generally declined among males and increased among females, except in Italy. Among males in E&W and Finland, SAM contributed 93% and 76% to declining absolute all-cause mortality inequalities, but this contribution varied over time. Among males in Italy, SAM drove the 1976-1992 increase in all-cause mortality inequalities. Among females in Finland, increasing inequalities in SAM hampered larger declines in mortality inequalities. CONCLUSION: Our findings demonstrate that differing education-specific SAM trends by country and sex result in different inequality trends, and consequent contributions of SAM on educational mortality inequalities. The following decades of the smoking epidemic could increase educational mortality inequalities among Finnish and Italian women.

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BACKGROUND: Understanding of ethnic disparities in suicide in England and Wales is poor as ethnicity is not recorded on death certificates. Using linked data, we examined variations, by sex, in suicide rates in England and Wales by ethnicity and migrant and descendant status. METHODS: Using the Office for National Statistics 2012-19 mortality data linked to the 2011 census from the Public Health Research Database, we calculated the age-standardised suicide rates by sex for each of the 18 self-identified ethnicity groups in England and Wales. We present rates by age, sex, and methods used for suicide by ethnic group. We estimated age-adjusted and sex-adjusted incidence rate ratios (IRRs) using Poisson regression models for each minority ethnic group compared with the majority population. We involved people with lived experience in the research. FINDINGS: Overall, 31 644 suicide deaths occurred over the study period, including 3602 (11%) in people from minority ethnic backgrounds, with a mean age of death of 43·3 years (SD 17·0, range 13-96). Almost all minority ethnic groups had a lower rate of suicide than the White British majority, apart from individuals who identified as being from a Mixed heritage background or White Gypsy or Irish Travellers. In females who identified as Mixed White and Caribbean, the suicide IRR was 1·79 (95% CI 1·45-2·21) compared with the White British majority; in those who identified as White Gypsy or Irish Travellers, the IRR was 2·26 (1·42-3·58). Rates in males identifying as from these two groups and those identifying as White Irish were similar to the White British majority. Compared with the non-migrant population, migrants had a lower rate of suicide regardless of ethnicity, but in the descendant population, people from a Mixed ethnicity background had a higher risk of suicide than the White British majority. INTERPRETATION: There are ethnic disparities in suicide mortality in England and Wales, but the reasons for this are unclear. The higher rate in previously overlooked minority ethnic groups warrants further attention. FUNDING: Wellcome Trust.

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The aim of this study was to identify risk factors for abdominal aortic aneurysm (AAA) from the largest Welsh screening cohort to date. Patients were recruited from 1993 (to 2015) as part of the South East Wales AAA screening programme through general practitioners. Demographic data and risk factors were collected by means of a self-report questionnaire. Statistical tests were performed to determine whether associations could be observed between AAA and potential risk factors. Odds ratios (OR) were also calculated for each of the risk factors identified. A total of 6879 patients were included in the study. Two hundred and seventy-five patients (4.0%) presented with AAA, of which 16% were female and 84% were male. Patients with AAA were older than the (no AAA) control group (p < 0.0001). The following risk factors were identified for AAA: family history of AAA (p < 0.0001); history of vascular surgery (p < 0.0001), cerebrovascular accident (p < 0.0001), coronary heart disease (p < 0.0001), diabetes (p < 0.0001), medication (p = 0.0018), claudication (p < 0.0001), smoking history (p = 0.0001) and chronic obstructive pulmonary disorder (p = 0.0007). AAA is associated with classical vascular risk factors, in addition to other less-well-documented risk factors including previous vascular surgery. These findings have practical implications with the potential to improve future clinical screening of patients in order to reduce AAA mortality.

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INTRODUCTION: Early-life medical and surgical interventions in babies born preterm and/or with surgical conditions influence later life health and educational outcomes. Obtaining long-term outcomes post-discharge to evaluate the impact of interventions is complex, expensive, and burdensome to families. Linkage of routinely collected data offers a feasible and cost-effective solution. The NeoWONDER research programme aims to describe the short and long-term health and educational outcomes for babies born preterm and/or with surgical conditions and evaluate the impact of neonatal care and interventions on later health and educational outcomes. METHODS AND ANALYSIS: We will include babies who received care in neonatal units in England and Wales, born between 2007-2020 with a gestational age below 32 weeks (approximately 100,000), and/or born between 2012-2020 (all gestations) with any of six surgical conditions: necrotising enterocolitis, Hirschsprung's disease, gastroschisis, oesophageal atresia, congenital diaphragmatic hernia, and posterior urethral valves (approximately 8,000). A detailed list of surgical condition codes is shown in S3 File. We will obtain long-term health and education outcomes through linkage of the National Neonatal Research Database, which contains routine data for all babies admitted to NHS neonatal units, to other existing health and educational datasets. For England, these are: Hospital Episode Statistics, the Office for National Statistics, Mental Health Services Dataset, Paediatric Intensive Care Audit Network, National Pupil Database; and for Wales, the Secure Anonymised Information Linkage databank. Analysis will be undertaken on de-identified linked datasets. Outcomes of interest for health include mortality, hospital admissions, diagnoses indicative of neurodisability and/or chronic illness, health care utilisation; and for education are attainment (using national curriculum assessments), school absence and special educational needs status.

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Aims: The COVID-19 pandemic has disrupted the provision of arthroplasty services in England, Wales, and Northern Ireland. This study aimed to quantify the backlog, analyze national trends, and predict time to recovery. Methods: We performed an analysis of the mandatory prospective national registry of all independent and publicly funded hip, knee, shoulder, elbow, and ankle replacements in England, Wales, and Northern Ireland between January 2019 and December 2022 inclusive, totalling 729,642 operations. The deficit was calculated per year compared to a continuation of 2019 volume. Total deficit of cases between 2020 to 2022 was expressed as a percentage of 2019 volume. Sub-analyses were performed based on procedure type, country, and unit sector. Results: Between January 2020 and December 2022, there was a deficit of 158,994 joint replacements. This is equivalent to over two-thirds of a year of normal expected operating activity (71.6%). There were 104,724 (-47.1%) fewer performed in 2020, 41,928 (-18.9%) fewer performed in 2021, and 12,342 (-5.6%) fewer performed in 2022, respectively, than in 2019. Independent-sector procedures increased to make it the predominant arthroplasty provider (53% in 2022). NHS activity was 73.2% of 2019 levels, while independent activity increased to 126.8%. Wales (-136.3%) and Northern Ireland (-121.3%) recorded deficits of more than a year's worth of procedures, substantially more than England (-66.7%). It would take until 2031 to eliminate this deficit with an immediate expansion of capacity over 2019 levels by 10%. Conclusion: The arthroplasty deficit following the COVID-19 pandemic is now equivalent to over two-thirds of a year of normal operating activity, and continues to increase. Patients awaiting different types of arthroplasty, in each country, have been affected disproportionately. A rapid and significant expansion in services is required to address the deficit, and will still take many years to rectify.

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BACKGROUND: In May 2020, England implemented soft 'opt-out' or 'deemed consent' for deceased donation with the intention of raising consent rates. However, this coincided with the COVID-19 pandemic, making it difficult to assess the early impact of the law change. Wales and Scotland changed their organ donation legislation to implement soft opt-out systems in 2015 and 2021 respectively. This study provides a descriptive analysis of changes in consent and transplant rates for deceased organ donation in England, Scotland and Wales. METHODS: Logistic regression and descriptive trend analysis were employed to assess the probability of a patient who died in critical care becoming a donor, and to report consent rates using data, respectively, from the Intensive Care National Audit and Research Centre (ICNARC) in England from 1 April 2014 to 30 September 2021, and from the Potential Donor Audit for England, Scotland and Wales from April 2010 to June 2023. RESULTS: The number of eligible donors in April-June 2020 were 56.5%, 59.3% and 57.6% lower in England, Scotland and Wales relative to April-June 2019 (pre-pandemic). By April-June 2023, the number of eligible donors had recovered to 87.4%, 64.2% and 110.3%, respectively, of their levels in 2019. The consent rate in England, Scotland and Wales reduced from 68.3%, 63.0% and 63.6% in April-June 2019 to 63.2%, 60.5% and 56.3% in April-June 2023. CONCLUSIONS: While the UK organ donation system shows signs of recovery from the COVID-19 pandemic, the number of eligible potential donors and consent rates remain below their pre-pandemic levels.

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BACKGROUND: Reinterventions may influence the outcomes of children with functionally single-ventricle (f-SV) congenital heart disease. METHODS AND RESULTS: We undertook a retrospective cohort study of children starting treatment for f-SV between 2000 and 2018 in England, using the national procedure registry. Patients were categorized based on whether they survived free of transplant beyond 1 year of age. Among patients who had transplant-free survival beyond 1 year of age, we explored the relationship between reinterventions in infancy and the outcomes of survival and Fontan completion, adjusting for complexity. Of 3307 patients with f-SV, 909 (27.5%), had no follow-up beyond 1 year of age, among whom 323 (35.3%) had ≥1 reinterventions in infancy. A total of 2398 (72.5%) patients with f-SV had transplant-free survival beyond 1 year of age, among whom 756 (31.5%) had ≥1 reinterventions in infancy. The 5-year transplant-free survival and cumulative incidence of Fontan, among those who survived infancy, were 93.4% (95% CI, 92.4%-94.4%) and 79.3% (95% CI, 77.4%-81.2%), respectively. Both survival and Fontan completion were similar for those with a single reintervention and those who had no reinterventions. Patients who had >1 additional surgery (adjusted hazard ratio, 3.93 [95% CI, 1.87-8.27] P<0.001) had higher adjusted risk of mortality. Patients who had >1 additional interventional catheter (adjusted subdistribution hazard ratio, 0.71 [95% CI, 0.52-0.96] P=0.03) had a lower likelihood of achieving Fontan. CONCLUSIONS: Among children with f-SV, the occurrence of >1 reintervention in the first year of life, especially surgical reinterventions, was associated with poorer prognosis later in childhood.

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BACKGROUND: There is limited data around drivers of changes in mortality over time. We aimed to examine the temporal changes in mortality and understand its determinants over time. METHODS: 743,149 PCI procedures for patients from the British Cardiovascular Intervention Society (BCIS) database who were aged between 18 and 100 years and underwent Percutaneous Coronary Intervention (PCI) for Acute Coronary Syndrome (ACS) in England and Wales between 2006 and 2021 were included. We decomposed the contributing factors to the difference in the observed mortality proportions between 2006 and 2021 using Fairlie decomposition method. Multiple imputation was used to address missing data. RESULTS: Overall, there was an increase in the mortality proportion over time, from 1.7% (95% CI: 1.5% to 1.9%) in 2006 to 3.1% (95% CI: 3.0% to 3.2%) in 2021. 61.2% of this difference was explained by the variables included in the model. ACS subtypes (percentage contribution: 14.67%; 95% CI: 5.76% to 23.59%) and medical history (percentage contribution: 13.50%; 95% CI: 4.33% to 22.67%) were the strongest contributors to the difference in the observed mortality proportions between 2006 and 2021. Also, there were different drivers to mortality changes between different time periods. Specifically, ACS subtypes and severity of presentation were amongst the strongest contributors between 2006 and 2012 while access site and demographics were the strongest contributors between 2012 and 2021. CONCLUSIONS: Patient factors and the move towards ST-elevated myocardial infarction (STEMI) PCI have driven the short-term mortality changes following PCI for ACS the most.

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PURPOSE: Despite a known risk of cellulitis recurrence, the management of the wider impact and risk factors has been neglected. The innovative National Cellulitis Improvement Programme (NCIP) addresses this by providing evidence-based and individualised care to improve patient reported outcomes and reduce the risk of recurrence. The aim of this paper is to examine the longer-term impact of cellulitis and to identify a suitable and clinically relevant Patient Reported Outcome Measure (PROM). METHODS: A review of existing cellulitis-specific PROMs was undertaken, alongside literature detailing the patient-focused impact of cellulitis, to identify a suitable PROM for clinical use. A group of expert therapists and patient representatives (n = 14) shared their individual and collective experiences over a series of events to discuss and debate the impact of cellulitis and review available PROMs. CELLUPROM© is introduced with anonymised PROM data and case study information reported to establish the impact of CELLUPROM© within usual NCIP care. RESULTS: No cellulitis-specific PROMs were identified. Literature focused on the signs and symptoms of an acute episode of cellulitis, with outcome measures primarily used to evidence the impact of an intervention. An enduring physical, social and emotional impact of cellulitis was identified in this study, providing the basis for the new cellulitis-specific PROM (CELLUPROM©), which has been implemented with good effect in clinical care. CONCLUSION: This study has highlighted the lasting impact of cellulitis. Using CELLUPROM© within the risk-reduction NCIP has helped develop Value-Based Healthcare and support programme evaluation.

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BACKGROUND: There is limited evidence on the safety of Hormone Replacement Therapy (HRT) in women with cancer. Therefore, we systematically examined HRT use and cancer-specific mortality in women with 17 site-specific cancers. METHODS: Women newly diagnosed with 17 site-specific cancers from 1998 to 2019, were identified from general practitioner (GP) records, hospital diagnoses or cancer registries in Scotland, Wales and England. Breast cancer patients were excluded because HRT is contraindicated in breast cancer patients. The primary outcome was time to cancer-specific mortality. Time-dependent Cox regression models were used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (95% CIs) for cancer-specific mortality by systemic HRT use. RESULTS: The combined cancer cohorts contained 182,589 women across 17 cancer sites. Overall 7% of patients used systemic HRT after their cancer diagnosis. There was no evidence that HRT users, compared with non-users, had higher cancer-specific mortality at any cancer site. In particular, no increase was observed in common cancers including lung (adjusted HR = 0.98 95% CI 0.90, 1.07), colorectal (adjusted HR = 0.79 95% CI 0.70, 0.90), and melanoma (adjusted HR = 0.77 95% CI 0.58, 1.02). CONCLUSIONS: We observed no evidence of increased cancer-specific mortality in women with a range of cancers (excluding breast) receiving HRT.

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OBJECTIVES: To compare the patterns of multimorbidity between people with and without rheumatic and musculoskeletal diseases (RMDs) and to describe how these patterns change by age and sex over time, between 2010 and 2019. PARTICIPANTS: 103 426 people with RMDs and 2.9 million comparators registered in 395 Wales general practices (GPs). Each patient with an RMD aged 0-100 years between January 2010 and December 2019 registered in Clinical Practice Research Welsh practices was matched with up to five comparators without an RMD, based on age, gender and GP code. PRIMARY OUTCOME MEASURES: The prevalence of 29 Elixhauser-defined comorbidities in people with RMDs and comparators categorised by age, gender and GP practices. Conditional logistic regression models were fitted to calculate differences (OR, 95% CI) in associations with comorbidities between cohorts. RESULTS: The most prevalent comorbidities were cardiovascular risk factors, hypertension and diabetes. Having an RMD diagnosis was associated with a significantly higher odds for many conditions including deficiency anaemia (OR 1.39, 95% CI (1.32 to 1.46)), hypothyroidism (OR 1.34, 95% CI (1.19 to 1.50)), pulmonary circulation disorders (OR 1.39, 95% CI 1.12 to 1.73) diabetes (OR 1.17, 95% CI (1.11 to 1.23)) and fluid and electrolyte disorders (OR 1.27, 95% CI (1.17 to 1.38)). RMDs have a higher proportion of multimorbidity (two or more conditions in addition to the RMD) compared with non-RMD group (81% and 73%, respectively in 2019) and the mean number of comorbidities was higher in women from the age of 25 and 50 in men than in non-RMDs group. CONCLUSION: People with RMDs are approximately 1.5 times as likely to have multimorbidity as the general population and provide a high-risk group for targeted intervention studies. The individuals with RMDs experience a greater load of coexisting health conditions, which tend to manifest at earlier ages. This phenomenon is particularly pronounced among women. Additionally, there is an under-reporting of comorbidities in individuals with RMDs.

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